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Cited by 369

The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.

Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2

Tevosian, Sergei G., Albrecht, Kenneth H., Crispino, John D., Fujiwara, Yuko, Eicher, Eva M., Orkin, Stuart H.·2002·Development

Abstract

In mammals, Sry expression in the bipotential, undifferentiated gonad directs the support cell precursors to differentiate as Sertoli cells, thus initiating the testis differentiation pathway. In the absence of Sry, or if Sry is expressed at insufficient levels, the support cell precursors differentiate as granulosa cells, thus initiating the ovarian pathway. The molecular mechanisms upstream and downstream of Sry are not well understood. We demonstrate that the transcription factor GATA4 and its co-factor FOG2 are required for gonadal differentiation. Mouse fetuses homozygous for a null allele of Fog2 or homozygous for a targeted mutation in Gata4 (Gata4ki) that abrogates the interaction of GATA4 with FOG co-factors exhibit abnormalities in gonadogenesis. We found that Sry transcript levels were significantly reduced in XY Fog2–/– gonads at E11.5, which is the time when Sry expression normally reaches its peak. In addition, three genes crucial for normal Sertoli cell function (Sox9, Mis and Dhh) and three Leydig cell steroid biosynthetic enzymes (p450scc, 3βHSD and p450c17) were not expressed in XY Fog2–/– and Gataki/ki gonads, whereas Wnt4, a gene required for normal ovarian development, was expressed ectopically. By contrast, Wt1 and Sf1, which are expressed prior to Sry and necessary for gonad development in both sexes, were expressed normally in both types of mutant XY gonads. These results indicate that GATA4 and FOG2 and their physical interaction are required for normal gonadal development.

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Crossref · 10.1242/dev.129.19.4627

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Metadata

Authors
Tevosian, S. G., Albrecht, K. H., Crispino, J. D., Fujiwara, Y., Eicher, E. M., & Orkin, S. H.
Venue
Development
Published
2002-10-01
Volume
129
Issue
19
Pages
4627-4634
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2155519853
Cited by
369
References
64
FWCI
8.67
Type
journal article
Language
en
Open access
closed

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